I would like to develop a molecular approach towards understanding the genetic behavior of multigene systems in higher organisms, using mouse and human ribosomal DNA (rDNA). I will first study the structure of the multiple copies or repeating units of these rDNAs using restriction enzyme analysis and other molecular methods. Any differences in molecular structure between repeats will then be used in studying the genetic behavior of these gene sequences. I will analyze the distribution of different repeat classes among the five chromosomes carrying rDNA in each species by classical genetic methods or by studying interspecific cell hybrids. I will use this accumulated molecular and genetic information to determine the basis for differences in rDNA structure and organization between individuals in natural populations of mice and men and between inbred mouse strains. I will also gather information on the genetic behavior of rDNA sequences in the mouse from studying the differences in rDNA structure between normal or neoplastic cell lines and the original inbred mouse strains from which these cell lines were derived. Analogous studies on human cell lines will also be made. I hope that studies on the molecular structure and chromosomal localization of the different human rDNA repeats will make a contribution to an understanding of human chromosomal abnormalities. It has been proposed that the interaction of rDNA sequences on both homologous and non-homologous chromosomes plays an important role in the etiology of Human D and G group chromosome syndromes. I hope to examine the extent to which this interaction is related to the structural type, rather than the absolute amount of rDNA present on each chromosome.